This competitive renewal application is based on a novel model which posits that partially distinct neural and cognitive mechanisms are involved in the etiology and developmental trajectory of attention-deficit/hyperactivity disorder (ADHD). We hypothesize that ADHD is due to a primary deficit in regulatory functions, most probably of subcortical origin, that is present early in ontogeny, remains relatively static throughout the lifetime, and is unrelated to the commonly-present, although highly variable, diminution of symptoms and impairment often seem over development. We hypothesize that the variation in diminution of symptoms and impairment frequently seen throughout development is in part related to the degree to which cortically-mediated neural systems can compensate for these early deficits through the use of "top-down" executive control. Using a large sample of "hyperactive/inattentive" and typically-developing control children who were recruited when they were 3-4 years-old and evaluated annually since then, this study will examine trajectories of ADHD symptoms over the school-age years to determine the relationship between changes in ADHD severity and the development of regulatory and executive functions over time. Children will be comprehensively reevaluated annually using clinical and neuropsychological measures between the ages of 8 and 12 years. In addition, these annual assessments will be supplemented by semi-annual parent and teacher ratings of ADHD symptom severity and impairment in the home and school settings, which will greatly facilitate our ability to conduct analyses of individualized trajectories for ADHD severity. The primary aim of the proposed project is to test the hypothesis that the diminution of ADHD symptoms typically seen over development is associated with the development of "top-down" executive processes, but that "bottom-up" regulatory functions will remain impaired irrespective of clinical improvement. If this hypothesis is confirmed, it could have a significant impact on the development of novel treatment interventions. PUBLIC HEALTH RELEVANCE: This project is designed to test a model that posits specific mechanisms that are linked to the improvement of ADHD severity over development as distinct from those that cause the disorder. If our hypothesis is confirmed, it could have a significant impact on the development of novel, long-lasting, treatment interventions for this highly impaired group of patients.